The hybridization of cultured human lymphocytes with a) mouse fibroblasts and b) human fibroblasts is proposed, using biochemically mutant human and murine cells. In the proposed experiments, we will attempt the separation of hybrids from parent cells by physical and chemical means, and will develop new mutants, especially ouabain-resistant lymphoblasts, for use in the hybridizations. The purpose of these studies is to determine how immunoglobulin synthesis is regulated in human cells and which chromosomes carry the genes for heavy and light chain synthesis.